Evidence map›Paper›PMID 34012783›Full record

ArticleTranslational lung cancer research2021

Conventional and semi-automatic histopathological analysis of tumor cell content for multigene sequencing of lung adenocarcinoma.

Daniel Kazdal, Eugen Rempel, Cristiano Oliveira, Michael Allgäuer, Alexander Harms, Kerstin Singer, Elke Kohlwes, Steffen Ormanns, Ludger Fink, Jörg Kriegsmann and 22 more

Open access · diamondAbstract read
In one paragraph

Article in Translational lung cancer research, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.

0numbers the graph read from it
0cells of the map it votes in
13citing papers in PubMed
0.9field-weighted citation impact, top 32% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

13 citing papers in PubMed, 15 citations in OpenAlex.

  1. Review
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  7. Digital counting of tissue cells for molecular analysis: the QuANTUM pipeline.Virchows Archiv : an international journal of pathology · 2025
    Article
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  10. Review
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  13. Biomarkers of response to checkpoint inhibitors beyond PD-L1 in lung cancer.Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc · 2022
    Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

32 authors at 8 institutions in 2 countries.

Daniel KazdalInstitute of Pathology, University Hospital Heidelberg, Heidelberg, Germany.
Eugen RempelInstitute of Pathology, University Hospital Heidelberg, Heidelberg, Germany.
Cristiano OliveiraInstitute of Pathology, University Hospital Heidelberg, Heidelberg, Germany.
Michael AllgäuerInstitute of Pathology, University Hospital Heidelberg, Heidelberg, Germany.
Alexander HarmsInstitute of Pathology, University Hospital Heidelberg, Heidelberg, Germany.
Kerstin SingerInstitute of Pathology, University Hospital Tübingen, Tübingen, Germany.
Elke KohlwesInstitute of Pathology, Johannes Gutenberg University Mainz, Mainz, Germany.
Steffen OrmannsInstitute of Pathology, Ludwig-Maximilians University of Munich, Munich, Germany.
Ludger FinkInstitute of Pathology, Cytopathology, and Molecular Pathology, UEGP MVZ, Giessen/Wetzlar/Limburg, Germany.
Jörg KriegsmannMVZ for Histology, Cytology and Molecular Diagnostics, Trier, Germany.
Michael LeichsenringJoint Practice for Pathology Gütersloh, Gütersloh, Germany.
Katharina KriegsmannDepartment of Hematology, Oncology and Rheumatology, University Hospital Heidelberg, Heidelberg, Germany.
Fabian StögbauerInstitute of Pathology, Technical University of Munich, Munich, Germany.
Luca TavernarInstitute of Pathology, University Hospital Heidelberg, Heidelberg, Germany.
Jonas LeichsenringInstitute of Pathology, University Hospital Heidelberg, Heidelberg, Germany.
Anna-Lena VolckmarInstitute of Pathology, University Hospital Heidelberg, Heidelberg, Germany.
Rémi LonguespéeDepartment of Clinical Pharmacology and Pharmacoepidemiology, University Hospital Heidelberg, Heidelberg, Germany.
Hauke WinterTranslational Lung Research Center (TLRC) Heidelberg, German Center for Lung Research (DZL), Heidelberg, Germany.
Martin EichhornTranslational Lung Research Center (TLRC) Heidelberg, German Center for Lung Research (DZL), Heidelberg, Germany.
Claus Peter HeußelDepartment of Thoracic Surgery, Thoraxklinik at University Hospital Heidelberg, Heidelberg, Germany.
Felix HerthTranslational Lung Research Center (TLRC) Heidelberg, German Center for Lung Research (DZL), Heidelberg, Germany.
Petros ChristopoulosTranslational Lung Research Center (TLRC) Heidelberg, German Center for Lung Research (DZL), Heidelberg, Germany.
Martin ReckTranslational Lung Research Center (TLRC) Heidelberg, German Center for Lung Research (DZL), Heidelberg, Germany.
Thomas MuleyTranslational Lung Research Center (TLRC) Heidelberg, German Center for Lung Research (DZL), Heidelberg, Germany.
Wilko WeichertInstitute of Pathology, Technical University of Munich, Munich, Germany.
Jan BudcziesInstitute of Pathology, University Hospital Heidelberg, Heidelberg, Germany.
Michael ThomasTranslational Lung Research Center (TLRC) Heidelberg, German Center for Lung Research (DZL), Heidelberg, Germany.
Solange PetersDepartment of Oncology, Centre Hospitalier Universitaire Vaudois (CHUV) and Lausanne University, Lausanne, Switzerland.
Arne WarthInstitute of Pathology, University Hospital Heidelberg, Heidelberg, Germany.
Peter SchirmacherInstitute of Pathology, University Hospital Heidelberg, Heidelberg, Germany.
Albrecht StenzingerInstitute of Pathology, University Hospital Heidelberg, Heidelberg, Germany.
Mark KriegsmannInstitute of Pathology, University Hospital Heidelberg, Heidelberg, Germany.
Heidelberg University · DEUniversity Hospital Heidelberg · DEGerman Center for Lung Research · DEJohannes Gutenberg University Mainz · DELudwig-Maximilians-Universität München · DETechnical University of Munich · DEMiele (Germany) · DEUniversity Children's Hospital Tübingen · DE

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundTargeted genetic profiling of tissue samples is paramount to detect druggable genetic aberrations in patients with non-squamous non-small cell lung cancer (NSCLC). Accurate upfront estimation of tumor cell content (TCC) is a crucial pre-analytical step for reliable testing and to avoid false-negative results. As of now, TCC is usually estimated on hematoxylin-eosin (H&E) stained tissue sections by a pathologist, a methodology that may be prone to substantial intra- and interobserver variability. Here we the investigate suitability of digital pathology for TCC estimation in a clinical setting by evaluating the concordance between semi-automatic and conventional TCC quantification.

methodsTCC was analyzed in 120 H&E and thyroid transcription factor 1 (TTF-1) stained high-resolution images by 19 participants with different levels of pathological expertise as well as by applying two semi-automatic digital pathology image analysis tools (HALO and QuPath).

resultsAgreement of TCC estimations [intra-class correlation coefficients (ICC)] between the two software tools (H&E: 0.87; TTF-1: 0.93) was higher compared to that between conventional observers (0.48; 0.47). Digital TCC estimations were in good agreement with the average of human TCC estimations (0.78; 0.96). Conventional TCC estimators tended to overestimate TCC, especially in H&E stainings, in tumors with solid patterns and in tumors with an actual TCC close to 50%.

conclusionsOur results determine factors that influence TCC estimation. Computer-assisted analysis can improve the accuracy of TCC estimates prior to molecular diagnostic workflows. In addition, we provide a free web application to support self-training and quality improvement initiatives at other institutions.

Indexed as

Digital pathologylung adenocarcinoma (lung ADC)molecular pathologynext-generation sequencing (NGS)tumor cell content (TCC)

Identifiers

PMID34012783
PMCPMC8107748
OpenAlexW3155296316

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.